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Compound Danshen dripping pills (CDDP), a well-known traditional Chinese medicine, is widely used to prevent and treat cardiovascular diseases. CDDP is usually prescribed in combination with clopidogrel (CLP), but the herb-drug interactions are rarely reported. This study evaluated the effects of CDDP on the pharmacokinetics and pharmacodynamics of coadministered CLP, and ensured the safety and efficacy of their usage. The trial design included a single-dose administration and multidose test for 7 consecutive days. Wistar rats received CLP alone or CLP combined with CDDP. After the final dose, plasma samples were collected at various time points, and the active metabolite H4 of CLP was analyzed by ultrafast liquid chromatography coupled with triple quadrupole tandem mass spectrometry. The main pharmacokinetic parameters of Cmax (maximum [or peak] serum concentration), Tmax (peak plasma time), t1/2 (half-time), AUC0-∞ (area under the concentration-time curve from dosing (time 0) to infinite time), and AUC0-t (area under the concentration-time curve from dosing [time 0] to time t) were calculated using the non-compartment model. In addition, prothrombin time, activated partial thromboplastin time, bleeding time, and adenosine diphosphate-induced platelet aggregation were evaluated for anticoagulation and antiplatelet aggregation activity. In this study, we found that CDDP had no significant effect on the metabolism of CLP in rats. In pharmacodynamic studies, the combination group showed significant synergistic antiplatelet activity compared with the CLP or CDDP groups alone. Based on pharmacokinetic and pharmacodynamic results, CDDP and CLP have synergistic effects on antiplatelet aggregation and anticoagulation.
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BACKGROUND: The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy. PURPOSE: To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case. METHODS: Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers. RESULTS: There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP. CONCLUSION: Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicina Tradicional China/métodos , Proteómica , Medicamentos Herbarios Chinos/química , Biomarcadores/análisisRESUMEN
The real-time cell-based assay(RTCA) was used to establish the bioelectrical sensing model of Compound Danshen Dripping Pills with rat cardiomyocytes(H9 c2). The time/dose-dependent cell response profiles(TCRPs) of in vitro dissolution and absorption of the pills were determined to establish the continuous dynamic dissolution and absorption kinetic models. Thereby, the cell index(CI)-based dissolution and absorption kinetic curves and kinetic models of Compound Danshen Dripping Pills were obtained. The optimal dissolution kinetic model was Weibull model. The similarity factors f_2 of dissolution curves were greater than 50 and the correlation coefficients of absorption curves were larger than 0.95. With the experiment about the efficacy on mice, percentages of the bleeding time of mice administrated with Compound Danshen Dripping Pills were calculated, and there was a correlation among dissolution, absorption, and efficacy curves(r > 0.9). RTCA is applicable to the study of the dissolution and absorption kinetics of solid compound Chinese medicine preparations. Thus, it is an innovative and feasible method to evaluate the quality and batch consistency of compound Chinese medicine preparations.
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Medicamentos Herbarios Chinos , Salvia miltiorrhiza , Ratas , Ratones , Animales , Solubilidad , Miocitos CardíacosRESUMEN
To systematically evaluate the clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy. China National Knowledge Infrastructure(CNKI), Wanfang, VIP, PubMed, EMbase, Cochrane Library, Ovid and Web of Science databases were searched by computer to retrieve the randomized controlled trials(RCTs) of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy from the establishment of databases to July 2020. After two researchers performed data retrieval, data extraction, and risk assessment of bias, they used RevMan 5.3 software for Meta-analysis. A total of 10 RCTs were included, with a total of 979 patients. Meta-analysis results showed that in terms of interventricular septal thickness(MD=-0.70, 95%CI[-1.15,-0.24], P=0.003), left ventricular posterior wall thickness(MD=-0.81, 95%CI[-1.41,-0.21], P=0.008), left ventricular mass index(MD=-8.75, 95%CI[-17.40,-0.10], P=0.05), systolic blood pressure(MD=-8.97, 95%CI[-13.46,-4.48], P<0.000 1), diastolic blood pressure(MD=-5.87, 95%CI[-8.39,-3.34], P<0.000 01) and left ventricular end-diastolic diameter(MD=-1.73, 95%CI[-2.38,-1.08], P<0.000 01), Compound Danshen Dripping Pills combined with conventional antihypertensive drugs was superior to conventional antihypertensive drugs. In terms of left ventricular ejection fraction(MD=0.41, 95%CI[-0.74, 1.55], P=0.49), there was no statistical difference in treatment between the two groups. Because of the small amount of literatures included in the safety aspect, it is impossible to give an accurate conclusion. The GRADE score showed that the level of evidence was low and extremely low. The results show that the Compound Danshen Dripping Pills combined with conventional antihypertensive drugs may effectively improve the clinical efficacy for hypertensive ventricular hypertrophy, and the safety needs to be further explored. Due to the low quality of the included literatures, more high-quality RCTs are needed for verification.
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Antihipertensivos , Medicamentos Herbarios Chinos , Antihipertensivos/efectos adversos , Canfanos , China , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Panax notoginseng , Salvia miltiorrhiza , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
China healthcare industry has gradually developed the consumer-centric integrated service model. To satisfy consumers' increasing demands on pluralistic, personalized and transparent healthcare services, pharmaceutical manufacturing enterprises must provide high-quality, precise and flexible medicines. This can be achieved by accelerating implementation of intelligent manufacturing, which is the core competitiveness of pharmaceutical manufacturing enterprises. According to the authors' intelligent manufacturing projects in a traditional Chinese medicine(TCM) factory, study and industrial practice on intelligent manufacturing were presented in this paper. First, the quality digitalization-based intelligent manufacturing methodology of TCM was proposed in this paper. The methodology mainly included three digitalized technologies in process and quality design, manufacturing process control and product batch evaluation. Next, the architectural design of intelligent manufacturing systems in one TCM factory was introduced, and the functional modules and data transmission relationships covering seedling, cultivation, herbal slices, preparation, storage and quality management systems were described. Finally, these technologies were fully used, and an integrated quality digitalization system was successfully established in the production workshop of a TCM product Compound Danshen Dripping Pills. The actual operation and application of process analyzers, supervisory control and data acquisition(SCADA), manufacturing execution system(MES), data analysis system, and enterprise resource planning system(ERP) were introduced. This paper provides reference for technical path planning and systematic architecture of TCM intelligent manufacturing.
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Medicina Tradicional China , Canfanos , China , Medicamentos Herbarios Chinos , Panax notoginseng , Control de Calidad , Salvia miltiorrhizaRESUMEN
INTRODUCTION: Clinical trials of Compound danshen dripping pills (CDDP) indicated distinct improvement in patients with chronic stable angina. Daily fluctuation of therapeutic effect agreed with a peak-valley PK profile during a 4-week CDDP regimen, but stabilized after 8-week treatment. OBJECTIVES: This article aims to explore the underlying mechanism for the time-dependent drug efficacy of the up-down fluctuation or stabilization in clinic trials. METHODS: A rat model of myocardial ischemia was established via isoproterenol induction. Metabolomics was employed to analyze the energy-related substances both in circulatory system and myocardium in the myocardial ischemia model. RESULTS: CDDP treatment ameliorated myocardial ischemia, reversed the reprogramming of the metabolism induced by ISO and normalized the level of most myocardial substrates and the genes/enzymes associated with those metabolic changes. After 1- or 2-week treatment, CDDP regulated plasma and myocardial metabolome in an analogous, time-dependent way, and modulated metabolic patterns of ischemic rats that perfectly matched with the fluctuated or stabilized effects observed in clinical trials with 4 or 8-week treatment, respectively. CONCLUSION: Metabolic modulation by CDDP contributes to the fluctuated or stabilized therapeutic outcome, and is a potential therapeutic approach for myocardial ischemia diseases.
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Medicamentos Herbarios Chinos/uso terapéutico , Metabolómica , Isquemia Miocárdica/tratamiento farmacológico , Animales , Canfanos , Estudios de Cohortes , Modelos Animales de Enfermedad , Femenino , Isoproterenol , Masculino , Isquemia Miocárdica/inducido químicamente , Isquemia Miocárdica/metabolismo , Panax notoginseng , Ratas , Ratas Sprague-Dawley , Salvia miltiorrhiza , Factores de TiempoRESUMEN
BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely. PURPOSE: It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process. METHODS: The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology. RESULTS: CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids. CONCLUSION: The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Infarto del Miocardio , Salvia miltiorrhiza , Medicamentos Herbarios Chinos/farmacología , Salvia miltiorrhiza/química , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Animales , Masculino , Farmacología en Red , Ratas Sprague-Dawley , Biomarcadores/metabolismo , Ratas , Lisofosfatidilcolinas , Canfanos , Panax notoginsengRESUMEN
BACKGROUND: Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. OBJECTIVE: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. METHODS: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. RESULTS: Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signaling pathways were notably enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, and TNF signaling pathway. Moreover, the molecular docking manifested excellent binding capacity between the active ingredients and targets on AP. CONCLUSION: This study comprehensively illustrated the bioactive, potential targets, and molecular mechanisms of CDDP against AP, offering fresh perspectives into the molecular mechanisms of CDDP in preventing and treating AP.
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Angina de Pecho , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Salvia miltiorrhiza , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Salvia miltiorrhiza/química , Angina de Pecho/tratamiento farmacológico , Angina de Pecho/metabolismo , Medicina Tradicional China , Canfanos , Panax notoginsengRESUMEN
BACKGROUD: Bidirectional communications between the gut microbiota and the brain may play a critical role in diabetes-related cognitive impairment. Compound Danshen Dripping Pills (CDDP) treatment has shown remarkable improvement in cognitive impairment in people with type 2 diabetes mellitus (T2DM) in clinical settings, but the underlying mechanisms remain unknown. PURPOSE: An extensive detailed strategy via in vivo functional experiments, transcriptomics, metabolomics, and network pharmacology was adopted to investigate the CDDP-treatment mechanism in diabetic cognitive dysfunction. METHODS: For 12 weeks, KK-Ay mice, a spontaneous T2DM model, were intragastrically administered various doses of CDDP solution or an equivalent volume of water, and the nootropic drug piracetam was orally administered as a positive control. At the 12th week, cognition was assessed using Morris water maze tests and brain magnetic resonance imaging (MRI). Furthermore, transcriptomics, metabolomics, and network pharmacology analyses were applied to reveal novel molecular mechanisms of CDDP-treatment in diabetic cognitive dysfunction of KK-Ay mice, which were then validated using quantitative real-time polymerase chain reaction and Western blot. RESULTS: Here we verified that CDDP can suppress inflammatory response and alleviate the cognitive dysfunction in KK-Ay mice. Also, as demonstrated by 16S rRNA sequencing and short-chain fatty acids (SCFAs) analysis, CDDP attenuated intestinal flora disorder as well as increases of metabolites including butyric acid, hexanoic acid, and isohexic acid. Given the integrated analyses of network pharmacology, transcriptomic, metabolomic data, and molecular biology, the TLR4/MyD88/NF-κB signaling pathway was activated in diabetes, which could be reversed by CDDP. CONCLUSIONS: Our findings demonstrate that CDDP restructures the gut microbiota composition and increased the intestinal SCFAs in KK-Ay mice, which might inhibit neuroinflammation, and thus improve diabetic mice cognitive disorder.
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Disfunción Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Ratones , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , FN-kappa B/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 4/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , ARN Ribosómico 16S , Disfunción Cognitiva/tratamiento farmacológico , Transducción de Señal , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Background: Long-term use of nitrates for treating stable angina pectoris (SAP) may lead to patients' tolerance to nitrates. As a traditional Chinese medicine, Compound danshen dropping pills (CDDP) is beneficial for patients with SAP. This study aimed to critically assess the efficacy and safety of CDDP vs. nitrates for SAP. Methods: PubMed, Embase, Web of Science, Cochrane library, CNKI, Wanfang Digital Periodicals, and Chinese Science and Technology Periodicals database were searched from inception to April 2023. Randomized controlled trials (RCTs) comparing CDDP with nitrates for SAP were included. The meta-analysis was conducted to estimate the pooled effect. Results: Twenty-nine studies were included for the statistical analysis. The meta-analyses with the random-effect model indicated that CDDP could significantly increase the effective rate in symptom improvement compared with nitrates (Pooled 9 RCTs, OR = 1.95, 95% CI: 1.25-3.05, P = 0.003, duration of 4 weeks; Pooled 4 RCTs, OR = 3.45, 95% CI: 1.84-6.48, P = 0.0001, duration of 6 weeks; Pooled 13 RCTs, OR = 4.02, 95% CI: 2.14-7.57, P < 0.0001, duration of 8 weeks). The meta-analyses with the random-effect model indicated that CDDP could significantly increase the effective rate in electrocardiogram improvement compared with nitrates (Pooled 5 RCTs, OR = 1.60, 95% CI: 1.02-2.52, P = 0.04, duration of 4 weeks; Pooled 3 RCTs, OR = 2.47, 95% CI: 1.60-3.82, P < 0.0001, duration of 6 weeks; Pooled 11 RCTs, OR = 3.43, 95% CI: 2.68-4.38, P < 0.00001, duration of 8 weeks). The incidence of adverse drug reactions in the CDDP group was lower than that in the nitrates group (Pooled 23 RCTs, OR = 0.15, 95% CI: 0.1-0.21, P < 0.00001). The results of the meta-analyses with fixed-effect model were similar with above results. The levels of the evidence ranged from very low to low. Conclusion: The present study suggests that CDDP with the duration of at least 4 weeks can be considered as an alternative to nitrates for treating SAP. However, more high-quality RCTs are still needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022352888, identifier [CRD42022352888].
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Background: Contrast-induced nephropathy (CIN) is one of the most common complications after coronary stent implantation due to the extensive development of coronary catheterization technology. Compound Danshen dripping pills (CDDP) are clinically used as cardiovascular drugs, relieving systemic inflammatory response. Previous studies have observed that CDDP can decrease CIN incidence after coronary stent implantation with uncertain effectiveness. Methods: We conducted a prospective, randomized, single-center, single-blind, controlled trial. We enrolled patients 18 years and older with unstable angina pectoris and NSTEMI who underwent PCI at the Tianjin Chest Hospital between November 1, 2021, and November 31, 2022, and followed for 30 days. Patients were randomized to CDDP and hydration therapy (10 capsules three times/day; N = 411) or hydration only (N = 411). The primary outcome was the contrast nephropathy incidence, defined as an elevation in serum creatinine by more than 25% or 44â µmol/L from baseline within 48-72â h of contrast exposure. Secondary outcomes included major adverse cardiovascular events post-surgery and during follow-up. Results: After 48â h of operation, the two groups had statistical significance in Scr and BUN values (80.0 ± 12.59 vs. 84.43 ± 13.49, P < 0.05; 6.22 ± 1.01 vs. 6.40 ± 0.93, P < 0.05). The difference in Scr in 72â h between the two groups was statistically significant (76.42 ± 10.92 vs. 79.06 ± 11.58, P < 0.05). The CIN incidence was significantly lower in the CDDP group than in the hydration group. The CIN risk was significantly elevated in patients with LVEF <50%, contrast volume ≥160â ml, and hypertension, after 48 and 72â h of operation. The serum inflammation index levels NGAL, TNF-α, oxidative stress indexes SOD, and MDA significantly differed between the two groups. However, there was no significant difference in serum apoptosis indexes Bax, Bcl-2, and Casepase-9. Conclusions: CDDP pre-treatment could prevent contrast-induced nephropathy. Inflammatory response and oxidative stress could be significant in the CDDP mechanism.
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BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
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Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/terapia , Volumen Sistólico , Remodelación Ventricular , Estudios Prospectivos , Microcirculación , Función Ventricular Izquierda , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/etiología , Resultado del Tratamiento , Intervención Coronaria Percutánea/efectos adversos , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Diabetic retinopathy (DR) is increasingly becoming a main complication of diabetes, and is difficult to cure. In our research, network pharmacology analysis suggested that both compound Danshen dripping pills (CDDP) and bezafibrate (BZF) have potential protective effects against DR and the two drugs may act synergistically. The pharmacological effects of the coadministration of CDDP and BZF were elucidated in db/db mice, which simulate DR. Fluorescein fundus angiography showed that coadministration attenuated vascular leakage. Optical coherence tomography and hematoxylin and eosin staining showed that coadministration improved retinal thickness better than CDDP monotherapy. In addition, cell fluorescence images of reactive oxygen species revealed that coadministration of CDDP and BZF had more potent effects against oxidative stress than CDDP monotherapy. Metabolomics analysis showed that coadministration reduced the ratio of oxidized glutathione to reduced glutathione further than CDDP monotherapy. Coadministration of CDDP and BZF may provide additional protective effects by resisting vascular leakage, increasing retinal thickness, and inhibiting inflammation and oxidative stress in DR.
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Introduction: Patients with incomplete revascularization (ICR) tend to develop refractory angina despite optimal medical therapy. The Compound Danshen Dripping Pills (CDDP) is a widely used antianginal drug in China and is shown to significantly alleviate myocardial ischemia. Previous studies showed dose-efficacy tendency when increasing doses of CDDP. This study aims to investigate the efficacy and safety of intensive doses of CDDP in patients with refractory angina with ICR. Methods and Analysis: The INCODER study is a multicenter, double-blind, randomized controlled, superiority trial. We plan to recruit 250 patients aged 18-85 years with a diagnosis of refractory angina with ICR. Patients will be randomized (1:1) to intensive treatment group (CDDP 20 pills three times per day) or standard treatment group (10 pills CDDP and 10 pills placebo three times per day). Patients will have a 6-week medication period and be followed up every 2 weeks. The primary endpoint is the change of total exercise time from baseline to week 6 as assessed by cardiopulmonary exercise testing (CPET). Secondary endpoints include changes in the frequency of angina, Canadian Cardiovascular Society angina class, nitroglycerin use, Seattle Angina Questionnaire scores, peak oxygen uptake (VO2 peak) and other parameters as measured by CPET, and the levels of plasma C-reactive protein, homocysteine, and N-terminal pro-B-type natriuretic peptide. Safety events related to CDDP use will be monitored. Ethics and Dissemination: The research had been approved by the Clinical research and laboratory animal ethics committee of the First Affiliated Hospital, Sun Yat-sen University ([2019]65). The results will be reported through peer-reviewed journals, seminars, and conference presentations. Trial Registration Number: www.chictr.org.cn (ChiCTR2000032384). Registered on 27 April 2020.
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BACKGROUND: Mild and systematically improving multiple metabolic disorders was a focused view for Compound Danshen Dripping Pills playing synergistic effects through multiple components and multiple targets. The difference in overall therapeutic effects and endogenous metabolic regulation between short- and long-term administration was still unclear. PURPOSE: This study aimed to explore the difference in endogenous metabolic regulation between short- and long-term Compound Danshen Dripping Pills (CDDP) administration against acute myocardial infarction (AMI). METHODS: The model of AMI was induced by ligating the left anterior descending coronary artery. The cardiac protection effects of CDDP were investigated by echocardiography, 1- or 2-week were defined as short- and long-term based on desirable efficacy variability. The entire metabolic changes between short- and long-term administration of CDDP were profiled by UPLC-Q-TOF-MS. In addition, the metabolic regulatory network of CDDP administration against myocardial infarction rats was also compared with those of a typical chemical drug isosorbide 5-mononitrate (ISMN). RESULTS: After 1- or 2-week continuous oral administration, CDDP could significantly alleviate AMI-induced cardiac dysfunction. By using LC-MS-based metabolomics analyses, we systematically investigated the metabolic profiles of plasma and heart tissue samples at fixed exposure time-points (2 h, 24 h) from AMI rats with CDDP treatment. Most interestingly, global endogenous metabolic changes were observed in cardiac samples collected at different stages post consecutive CDDP administration, fluctuating at 2 and 24 h after 1 week but stabilizing after 2 weeks. The disrupted metabolic pathways such as glycerophospholipid, amino acids, fatty acids, and arachidonic acid metabolism were reconstructed after both short- and long-term CDDP treatment, while taurine and hypotaurine metabolism and purine metabolism contributed to the whole efficacy after long-term CDDP administration. CONCLUSION: Long-term CDDP treatment plays prolonged and stable efficacy against AMI compared with short-term treatment by specifically regulating purine and taurine and hypotaurine metabolism and systematically redressing metabolic disorders.
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Medicamentos Herbarios Chinos , Infarto del Miocardio , Salvia miltiorrhiza , Animales , Canfanos , Cromatografía Liquida , Medicamentos Herbarios Chinos/química , Metabolómica , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Panax notoginseng , Purinas , Ratas , Salvia miltiorrhiza/química , Espectrometría de Masas en Tándem , TaurinaRESUMEN
BACKGROUND: The Compound Danshen Dripping Pills have been widely used in the treatment of diabetic retinopathy (DR), but there is a lack of systematic review of reports on this topic. To explore the efficacy of Compound Danshen Dripping Pills combined with western medicine in the treatment of diabetic retinopathy, we conducted a meta-analysis. METHODS: Randomized controlled trials published in the Chinese Medical Literature Database (CBM), Embase, PubMed, and Medline databases from January 2010 to August 2021 were searched. After screening the qualified literature, literature quality was evaluated by the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was performed on outcome measures including effective rate, visual field gray value, hemangioma volume, hemorrhagic plaque area, and visual acuity after diabetic retinopathy treatment with Compound Danshen Dripping Pills using Revman 5.3 analysis software to comprehensively evaluate the utility of Compound Danshen Dripping Pills. RESULTS: A total of 167 documents were preliminarily searched, and 8 studies involving 524 patients were included for meta-analysis. Meta-analysis showed that the statistical value of the effective rate of diabetic retinopathy treatment in the intervention group and control group was OR =5.00, 95% CI: 2.84, 8.83, P<0.0001. The statistical value of visual field gray value comparison was MD =-0.93, 95% CI: -0.98, -0.89, P<0.00001. The statistical value of hemangioma volume was MD =-3.16, 95% CI: -3.48, -2.84, P<0.00001. The statistical value of hemorrhagic plaque area comparison was MD =-0.65, 95% CI: -0.97, -0.32, P<0.0001. The statistical value of visual acuity comparison was MD =0.15, 95% CI: 0.10, 0.19, P<0.00001. DISCUSSION: The Compound Danshen Dripping Pills combined with western medicine are effective and safe in the treatment of diabetic retinopathy.
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Diabetes Mellitus , Retinopatía Diabética , Medicamentos Herbarios Chinos , Canfanos , Retinopatía Diabética/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Panax notoginseng , Ensayos Clínicos Controlados Aleatorios como Asunto , Salvia miltiorrhizaRESUMEN
OBJECTIVE: To analyze the efficacy and safety of compound Danshen dripping pills (CDDPs) in the treatment of patients with diabetic retinopathy (DR) with the syndrome of Qi stagnation and blood stasis. METHODS: The clinical data of 81 patients with DR admitted to our hospital were analyzed retrospectively, and the patients were divided into an observation group (n=40) and a control group (n=41) in accordance with a random number table. The observation group was treated with CDDPs, while the control group was treated with Captopril. The response rates, change of severity degrees of retinopathy, improvement of vision, incidence of macular edema and symptom scores were compared between the two groups. RESULTS: (1) The ratio of decreasing degree of severity of retinopathy in the observation group was greater than that in the control group, while the ratio of increasing degree of severity of retinopathy in the observation group was lower than that in the control group (P < 0.05). There was no significant difference in the constant ratio of degree of severity of retinopathy between the two groups (P > 0.05). (2) After treatment, the scores for dim vision, somber facial complexion, dry eyes, encrusted skin and numbness of the limbs in the observation group were lower than those in the control group (P < 0.05). (3) The overall response rates (ORRs) were 87.50% and 63.41% in the observation group and the control group, respectively (P < 0.05). (4) After treatment, the vision in the left and right eye in the observation group was higher than those in the control group (P < 0.05). (5) The incidence rates of macular edema were 12.50% and 31.71% in the observation group and the control group, respectively (P < 0.05). CONCLUSION: CDDPs can effectively elevate the response rate, reduce the degree of severity of retinopathy, mitigate the incidence of macular edema, and improve the vision of DR patients with the syndrome of Qi stagnation and blood stasis, exhibiting a satisfactory safety profile. Therefore, it has a good application value.
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BACKGROUND: Cases with no-reflow increased significantly and accounted for about 5-50% of cases in primary percutaneous coronary intervention (PPCI) patients in recent years. It is important to identify patients at high risk of no-reflow. Ingredients of compound danshen dripping pills (CDDP), a popular Chinese traditional medicine, can alleviate myocardial ischemia, inhibit inflammation and angiotensin convert enzyme, and reduce cell apoptosis, among other effects. In this study, we aimed to assess whether long-term treatment with CDDP (>1 year, could reduce the no-reflow phenomenon in non-diabetes mellitus (DM) patients after PPCI for acute myocardial infarction (AMI). METHODS: We enrolled patients according to inclusion and exclusion criteria. Clinical and PPCI data were collected. Patients were divided into 2 groups according to history of CDDP therapy. Data of the CDDP group and non-CDDP group were compared. Single and multivariate analysis was used to find factors associated with no-reflow. RESULTS: Among these 399 patients, the no-reflow phenomenon occurred in 96 patients (24.1%). The results showed that patients with long-term CDDP treatment had lower incidence of no-reflow than those without CDDP treatment within 1 year (9/68 vs. 87/331, 13.2% vs. 26.3%, P=0.0219). Univariate and multivariate stepwise logistic regression analysis identified a few admission parameters associated with the no-reflow phenomenon: prior myocardial infarction (MI) [odds ratio (OR) 3.13, 95% CI: 1.42-4.89], systolic blood pressure (SBP) <100 mmHg (OR 1.78, 95% CI: 1.28-4.06), cardiac troponin T (cTnT) (OR 1.78, 95% CI: 1.28-4.06), high-sensitivity C-reactive protein (hs-CRP) (OR 1.08, 95% CI: 1.01-1.15), brain natriuretic peptide (BNP) (OR 3.76, 95% CI: 1.31-9.75), interleukin-6 (IL-6) (OR 1.42, 95% CI: 1.17-3.29), ejection fraction (EF) (OR 1.39, 95% CI: 1.09-3.28), left ventricular end-diastolic diameter (LVEDD) (OR 1.28, 95% CI: 1.05-4.23), anterior wall infarction (OR 2.83, 95% CI: 1.69-5.76), and long-term CDDP treatment (OR 0.44, 95% CI: 0.89-0.21). CONCLUSIONS: Prior MI, SBP, cTnT, hs-CRP, BNP, and IL-6 on admission, along with EF, LVEDD, and anterior wall infarction are all predictors for no-reflow phenomenon. Long-term treatment with CDDP can reduce no-reflow phenomenon.
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Medicamentos Herbarios Chinos , Infarto del Miocardio , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Canfanos , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Infarto del Miocardio/tratamiento farmacológico , Panax notoginseng , Salvia miltiorrhizaRESUMEN
PURPOSE: The combination of warfarin and compound Danshen dripping pill (CDDP) is helpful for patients with both coronary heart disease (CHD) and atrial fibrillation (AF). The main adverse drug reaction of warfarin is bleeding because of its narrow therapeutic index. The safety of a combination therapy with warfarin and CDDP is always a concern. Our previous research showed that the combination of warfarin and CDDP improved the quality of life for patients with both CHD and AF. This study describes the changes in dose and concentration of warfarin necessary and evaluates bleeding risk when warfarin is given concomitantly with CDDP. METHODS: An ultra-performance liquid chromatography-MS/MS method with a chiral column was developed to assay the concentration of S-warfarin and R-warfarin in human plasma simultaneously. The method was applied to compare the concentration of warfarin in patients taking warfarin combined with CDDP and without CDDP. International normalized ratio (INR) values were monitored to evaluate bleeding risk. Paired t tests were then used to compare the dose and the concentration in 2 periods. Moreover, patients with VKORC1, CYP2C9*3, CYP4F2, EPHX1, and PROC gene polymorphisms were evaluated to determine interactions. FINDINGS: The results indicate that the dose of warfarin had no significant change with or without CDDP. Also, the peak concentrations of S-warfarin and total warfarin were significantly different in CYP4F2 C/C patients, but there was no significant difference identified in other genetic groups. No bleeding occurred in the study. IMPLICATIONS: The dose of warfarin would be sustainable when combined with CDDP, because CDDP did not affect concentration of warfarin significantly in most patients and the change of INR was not significant. CHINA CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-ONRC-13003523.
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Medicamentos Herbarios Chinos/farmacocinética , Cardiopatías/genética , Polimorfismo Genético/genética , Warfarina , Canfanos , Familia 4 del Citocromo P450/genética , Cardiopatías/tratamiento farmacológico , Hemorragia/inducido químicamente , Hemorragia/genética , Interacciones de Hierba-Droga , Humanos , Panax notoginseng , Salvia miltiorrhiza , Warfarina/administración & dosificación , Warfarina/efectos adversos , Warfarina/farmacocinética , Warfarina/uso terapéuticoRESUMEN
As one of the main constituents of Compound Danshen Dripping Pills (CDDP), Panax notoginseng (PN) plays a pivotal role in the treatment of cardiovascular diseases. Numerous researches have proved that the dammarane type saponins including notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1) and ginsenoside Rb1 (GRb1) are the main bioactive components of PN in CDDP. An efficient, realiable and sensitive liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis method for simultaneously detecting NR1, GRg1 and GRb1 in human plasma was established and applied to the pharmacokinetics study of the three PN saponins after oral administration of CDDP. The human plasma samples were processed using acetonitrile and the target materials were separated on an Eclipse plus C18 column (100 × 4.6 mm, 3.5 µm) with a gradient mobile phase consisted of water (containing 0.1% formic acid) and methanol. Within the concentration ranges of 0.25-50 ng/mL, each calibration curve exhibited an excellent linear relationship (r>0.998). The precision deviations of intra-day and inter-day analysis were lower than 9.0%, and accuracy error (RE%) ranged between 1.5% and 10.5%. The average recoveries of analytes were >64.0%. The established method was successfully applied to determine the pharmacokinetics of the three saponins in human plasma. In addition to providing guidance for clinical safe medication, the experimental results also provided a valuable and reliable basis for further pharmacological studies of PN in the human body after oral administration of CDDP.